Devices, systems, and methods to obtain conductance and temperature data

ABSTRACT

Devices, systems, and methods to measure parallel tissue conductance, luminal cross-sectional areas, fluid velocity, and/or determine plaque vulnerability using temperature. In at least one embodiment of a method to obtain parallel tissue conductance, the method comprises the steps of inserting at least part of a detection device into a luminal organ, applying current thereto, obtaining a native temperature measurement, injecting a solution of a known conductivity into the luminal organ, detecting a temperature change indicative of the fluid within the luminal organ, measuring an output conductance, and calculating a parallel tissue conductance based upon the output conductance and the conductivity of the injected solution.

PRIORITY

The present application is related to, claims the priority benefit of,and is a U.S. continuation patent application of, U.S. patentapplication Ser. No. 15/168,723, filed May 31, 2016 and issued as U.S.Pat. No. 10,213,129 on Feb. 26, 2019, which is related to, claims thepriority benefit of, and is a U.S. continuation patent application of,U.S. patent application Ser. No. 14/258,920, filed Apr. 22, 2014 andissued as U.S. Pat. No. 9,351,661 on May 31, 2016, which is related to,claims the priority benefit of, and is a U.S. continuation patentapplication of, U.S. Patent Application Ser. No. 12/701,368, filed Feb.5, 2010 and issued as U.S. Pat. No. 8,706,209 on Apr. 22, 2014. Thecontents of the foregoing patent applications and patents are herebyincorporated by reference in their entirety into this disclosure.

BACKGROUND

Coronary heart disease (CHD) is commonly caused by atheroscleroticnarrowing of the coronary arteries and is likely to produce anginapectoris, heart attacks or a combination. CHD caused 466,101 deaths inthe USA in 1997 and is one of the leading causes of death in Americatoday. To address CHD, intra-coronary stents have been used in largepercentages of CHD patients. Stents increase the minimal coronary lumendiameter to a greater degree than percutaneous transluminal coronaryangioplasty (PTCA) alone.

Intravascular ultrasound is a method of choice to determine the truediameter of a diseased vessel in order to size the stent correctly. Thetomographic orientation of ultrasound enables visualization of the full360° circumference of the vessel wall and permits direct measurements oflumen dimensions, including minimal and maximal diameter andcross-sectional area. Information from ultrasound is combined with thatobtained by angiography. Because of the latticed characteristics ofstents, radiographic contrast material can surround the stent, producingan angiographic appearance of a large lumen, even when the stent strutsare not in full contact with the vessel wall. A large observationalultrasound study after angiographically guided stent deployment revealedan average residual plaque area of 51% in a comparison of minimal stentdiameter with reference segment diameter, and incomplete wall appositionwas frequently observed. In this cohort, additional balloon inflationsresulted in a final average residual plaque area of 34%, even though thefinal angiographic percent stenosis was negative (20.7%). Thoseinvestigators used ultrasound to guide deployment.

However, using intravascular ultrasound as mentioned above requires afirst step of advancement of an ultrasound catheter and then withdrawalof the ultrasound catheter before coronary angioplasty thereby addingadditional time to the stent procedure. Furthermore, it requires anultrasound machine. This adds significant cost and time and more risk tothe procedure.

One common type of coronary artery disease is atherosclerosis, which isa systemic inflammatory disease of the vessel wall that affects multiplearterial beds, such as aorta, carotid and peripheral arteries, andcauses multiple coronary artery lesions and plaques. Atheroscleroticplaques typically include connective tissue, extracellular matrix(including collagen, proteoglycans, and fibronectin elastic fibers),lipid (crystalline cholesterol, cholesterol esters and phospholipids),and cells such as monocyte-derived macrophages, T lymphocytes, andsmooth muscles cells. A wide range of plaques occurs pathologically withvarying composition of these components.

A process called “positive remodeling” occurs early on during thedevelopment of atherosclerosis in coronary artery disease (CAD) wherethe lumen cross-sectional area (CSA) stays relatively normal because ofthe expansion of external elastic membrane and the enlargement of theouter CSA. However, as CAD progresses, there is no further increase inthe external diameter of the external elastic membrane. Instead, theplaque begins to impinge into the lumen and decreases the lumen CSA in aprocess called “negative remodeling”.

Evidence shows that that a non-significant coronary atheroscleroticplaque (typically <50% stenosis) can rupture and produce myocardialinfarct even before it produces significant lumen narrowing if theplaque has a particular composition. For example, a plaque with a highconcentration of lipid and a thin fibrous cap may be easily sheared orruptured and is referred to as a “vulnerable” plaque. In contrast,“white” plaques are less likely to rupture because the increased fibrouscontent over the lipid core provides stability (“stable” plaque). Alarge lipid core (typically >40%) rich in cholesterol is at a high riskfor rupture and is considered a “vulnerable” plaque. In summary, plaquecomposition appears to determine the risk of acute coronary syndromemore so than the standard degree of stenosis because a higher lipid coreis a basic characteristic of a higher risk plaque.

Conventionally, angiography has been used to visualize and characterizeatherosclerotic plaque in coronary arteries. Because of the recentfinding that plaque composition, rather than severity of stenosis,determines the risk for acute coronary syndromes, newer imagingmodalities are required to distinguish between and determine thecomposition of “stable” and “vulnerable” plaques. Although a number ofinvasive and noninvasive imaging techniques are available to assessatherosclerotic vessels, most of the standard techniques identifyluminal diameter, stenosis, wall thickness and plaque volume. To date,there is no standard method that can characterize plaque composition(e.g., lipid, fibrous, calcium, or thrombus) and therefore there is noroutine and reliable method to identify the higher risk plaques.

Noninvasive techniques for evaluation of plaque composition includemagnetic resonance imaging (MRI). However, MRI lacks the sufficientspatial resolution for characterization of the atherosclerotic lesion inthe coronary vessel. Minimally invasive techniques for evaluation ofplaque composition include intravascular ultrasound (IVUS), opticalcoherence tomography (OCT), raman and infrared spectroscopy.Thermography is also a catheter-based technique used to detect thevulnerable plaques on the basis of temperature difference caused by theinflammation in the plaque. Using the various catheter-based techniquesrequires a first step of advancement of an IVUS, OCT, or thermographycatheter and then withdrawal of the catheter before coronary angioplastythereby adding additional time and steps to the stent procedure.Furthermore, these devices require expensive machinery and parts tooperate. This adds significant cost arid time and more risk to theprocedure.

Thus, a need exists in the art for an alternative to the conventionalmethods of determining cross-sectional area of a luminal organ anddetermining the vulnerability of a plaque present within a luminalorgan. A further need exist for a reliable, accurate and minimallyinvasive system or technique of determining the same.

BRIEF SUMMARY

In at least one embodiment of a method to obtain a parallel tissueconductance within a luminal organ of the present disclosure, the methodcomprises the steps of introducing at least part of a detection deviceinto a luminal organ at a first location, the detection device having adetector and a thermistor positioned relative to the detector, applyingcurrent to the detection device using a stimulator, obtaining a firsttemperature measurement of a fluid native to the first location,injecting a solution having a known conductivity into the luminal organat or near the detector of the detection device, detecting a temperaturechange at the first location indicative of the injected solution,measuring an output conductance in connection with the injected solutionbased upon the detected temperature change, and calculating a paralleltissue conductance at the first location based in part upon the outputconductance and the conductivity of the injected solution. In at leastanother method, the step of calculating a parallel tissue conductancecomprises the step of calculating a cross-sectional area of the luminalorgan at the first location.

In at least one embodiment of a method to assess the vulnerability of aplaque within a luminal organ of the present disclosure, the methodcomprises the steps of introducing at least part of a detection deviceinto a luminal organ at a plaque site, the detection device having athermistor, injecting a solution into the luminal organ at or near thethermistor of the detection device, detecting a first temperaturemeasurement at the plaque site indicative of a plaque and the injectedsolution, and determining vulnerability of the plaque at the plaque sitebased in part upon the first temperature at the plaque site. In at leastone embodiment, the step of detecting a first temperature measurement isperformed using the thermistor.

In at least one embodiment of a device to obtain a parallel tissueconductance within a luminal organ of the present disclosure, the devicecomprises an elongated body having a longitudinal axis extending from aproximal end to a distal end, a pair of excitation electrodes located onthe elongated body, a pair of detection electrodes located on theelongated body in between the pair of excitation electrodes, and athermistor positioned along the longitudinal axis, located near thedistal end and positioned proximal to the first excitation electrode andthe second excitation electrode. In at least another embodiment, atleast one excitation electrode of the pair of excitation electrodesis/are in communication with a current source operable to supplyelectrical current to the at least one excitation electrode. In anotherembodiment, the device further comprises a data acquisition andprocessing system capable of receiving conductance data from the pair ofdetection electrodes, wherein, in at least one embodiment, the dataacquisition and processing system is further capable of calculating aparallel tissue conductance based in part upon the conductance data anda known conductivity of a solution injected into a luminal organ at ornear the pair of detection electrodes.

In at least one embodiment of a device to assess the vulnerability of aplaque within a luminal organ of the present disclosure, the devicecomprise an elongated body having a longitudinal axis extending from aproximal end to a distal end, and a thermistor positioned along thelongitudinal axis located near the distal end of the elongated body. Inat least another embodiment, the device further comprises a dataacquisition and processing system capable of receiving temperature datafrom the thermistor.

In at least one embodiment of a system to obtain a parallel tissueconductance within a luminal organ of the present disclosure, the systemcomprises a detection device having a detector and a thermistorpositioned relative to the detector, and a current source coupled to thedetector and the thermistor.

In at least one embodiment of a system to assess the vulnerability of aplaque within a luminal organ of the present disclosure, the systemcomprises an elongated body having a longitudinal axis extending from aproximal end to a distal end, a thermistor positioned along thelongitudinal axis located near the distal end of the elongated body, anda thermistor excitation device coupled to the thermistor.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B show at least a portion of an exemplary detectiondevices for obtaining parallel tissue conductance, measuring luminalcross-sectional areas, measuring fluid velocity, and/or determiningplaque vulnerability using temperature within a luminal organ, saiddevice having a thermistor, according to an embodiment of the presentdisclosure;

FIG. 1C shows an exemplary circuit diagram in connection with anexemplary device and/or system of the present disclosure;

FIG. 1D shows another embodiment of at least a portion of an exemplarydetection devices for obtaining parallel tissue conductance, measuringluminal cross-sectional areas, measuring fluid velocity, and/ordetermining plaque vulnerability using temperature within a luminalorgan, said device having a thermistor, according to an embodiment ofthe present disclosure;

FIG. 2A shows an exemplary system for obtaining parallel tissueconductance, measuring luminal cross-sectional areas, measuringfluid-velocity, and/or determining plaque vulnerability usingtemperature within a luminal organ, according to an embodiment of thepresent disclosure;

FIG. 2B shows an exemplary detection device of an exemplary systemhaving impedance measuring electrodes supported in front of a stentingballoon thereon, according to an embodiment of the present disclosure;

FIG. 2C shows an exemplary detection device of an exemplary systemhaving impedance measuring electrodes within and in front of a balloonthereon, according to an embodiment of the present disclosure;

FIG. 2D shows an exemplary detection device of an exemplary having anultrasound transducer within and in front of a balloon thereon,according to an embodiment of the present disclosure;

FIG. 2E shows an exemplary detection device of an exemplary systemwithout a stenting balloon, according to an embodiment of the presentdisclosure;

FIG. 2F shows an exemplary detection device of an exemplary systemhaving wire and impedance electrodes, according to an embodiment of thepresent disclosure;

FIG. 2G shows an exemplary detection device of an exemplary systemhaving multiple detection electrodes, according to an embodiment of thepresent disclosure;

FIGS. 2H and 2I show at least a portion of exemplary systems accordingto embodiments of the present disclosure;

FIG. 2J shows another exemplary system for obtaining parallel tissueconductance, measuring luminal cross-sectional areas, measuring fluidvelocity, and/or determining plaque vulnerability using temperaturewithin a luminal organ, according to an embodiment of the presentdisclosure;

FIG. 2K shows at least a portion of an exemplary detection device fordetermining plaque vulnerability using temperature within a luminalorgan, said device having a thermistor, according to an embodiment ofthe present disclosure;

FIGS. 3A-4B show steps of exemplary methods for obtaining paralleltissue conductance, measuring luminal cross-sectional areas, measuringfluid velocity, and/or determining plaque vulnerability usingtemperature within a luminal organ, according to various embodiments ofthe present disclosure;

FIG. 5A shows a balloon distension of the lumen of a coronary arteryaccording to an embodiment of the present disclosure;

FIG. 5B shows a balloon distension of a stent into the lumen of acoronary artery according to an embodiment of the present disclosure;

FIG. 6 shows a graph demonstrating the use of an exemplary device and/orsystem of the present disclosure; and

FIG. 7 shows steps of an exemplary method for obtaining parallel tissueconductance, measuring luminal cross-sectional areas, measuring fluidvelocity, and/or determining plaque vulnerability using temperaturewithin a luminal organ, according to an embodiment of the presentdisclosure.

DETAILED DESCRIPTION

For the purposes of promoting an understanding of the principles of thepresent disclosure, reference will now be made to the embodimentsillustrated in the drawings, and specific language will be used todescribe the same. It will nevertheless be understood that no limitationof the scope of this disclosure is thereby intended.

At least a portion of an exemplary embodiment of a device for obtainingparallel tissue conductance, measuring luminal cross-sectional areas,measuring fluid velocity, and/or determining plaque vulnerability usingtemperature of the present disclosure is shown in FIG. 1A. As shown inFIG. 1A, an exemplary device 100 comprises a detector 204 for detectingconductance within a luminal organ. Detector 204, along with othercomponents of device 100, are shown in an enlarged view in FIG. 1Anoting that, for example, device 100 may comprise any number ofcatheters or wires with the components referenced herein, including, butnot limited to, pressure wires, guide wires, or guide catheters.Detector 204, in at least one embodiment, is positioned along anelongated body 202 of device 100, wherein elongated body 202 has alongitudinal axis, a proximal end (further from detector 204), and adistal end (closer to detector 204).

In at least one embodiment of a device 100 of the present application,detector 204 is positioned along elongated body 202 of device 100 at ornear the distal end (“tip”) 19 of device 100. In an exemplaryembodiment, and as shown in FIG. 1A, detector 204 of device 100comprises detection electrodes 26, 28 positioned in between excitationelectrodes 25, 27, wherein excitation electrodes 25, 27 are capable ofproducing an electrical field. As shown in FIG. 1A, excitationelectrodes 25, 27 may comprise wires 25A and 27A, respectively, coupledthereto to facilitate the operation of excitation electrodes 25, 27 by auser. Similarly, detection electrodes 26, 28 may comprise wires 26A and28A, respectively, coupled thereto to facilitate the operation ofdetection electrodes 26, 28 by a user. Wires 25A, 26A, 27A, and 28A mayfurther couple to system console 250 (as shown in FIG. 2) so that, forexample, activation of excitation electrodes 25, 27 and the acquisitionof conductance information from detection electrodes 26, 28 may becontrolled.

As shown in FIG. 1A, an exemplary device 100 of the present disclosurecomprises a thermistor (temperature sensor) 102 coupled thereto, wherebythermistor 102 is connected to, for example, console 250 (as shown FIG.2) by way of thermistor wires 102A and 102B. Thermistor wires 102A and102B, as well as wires 25A, 26A, 27A, and 28A, may be coupled to console250, as referenced above, or to any number of other components of anexemplary system 200 of the present disclosure so that thermistor 102,excitation electrodes 25, 27, and detection electrodes 26, 28 mayoperate and/or provide data to user in accordance with the presentdisclosure. In an exemplary embodiment, thermistor wire 102A providescurrent to thermistor 102 to allow thermistor 102 to operate and detecttemperature, while thermistor wire 102B provides temperature data toconsole 250, or vice versa. In at least one embodiment of a device 100,wires 25A, 26A, 27A, 28A, 102A and/or 102B may have insulated electricalwire connections that run through, for example, a lumen of device 100and the proximal end of elongated body 102. In at least anotherembodiment, wires 25A, 26A, 27A, 28A, 102A and/or 102B may be embeddedwithin elongated body 102 so that each wire is insulated from the otherwires.

Another exemplary embodiment of at least part of an exemplary device 100of the present disclosure is shown in FIG. 1B. As shown in FIG. 1B,device 100 comprises the same/similar arrangement of electrodes 25, 26,27, and 28 and corresponding wires 25A, 26A, 27A, and 28A. However, inat least this exemplary embodiment, thermistor 102 shares, for example,wire 25A with excitation electrode 25, so that wire 25A provides currentto excitation electrode 25 and thermistor 102. As such, and as shown inFIG. 1B, wire 102A, for example, may connect thermistor 102 to console250 (not shown) or another portion of device 100/system 200 (asreferenced herein), so transmit temperature data from thermistor 102. Aswire 25A is shared between excitation electrode 25 and thermistor 102,the arrangement of electrodes and wires as shown in FIG. 1B is moreefficient than the arrangement shown in FIG. 1A.

An electrical circuit diagram consistent with the arrangement ofelectrodes and wires shown in FIG. 1B is shown in FIG. 1C. As shown inFIG. 1C, an exemplary circuit 90 may comprise any number of componentsso that thermistor 102 and excitation electrode 25 and/or 27 may operateas described above, For example, and as shown in FIG. 1C, circuit 90 maycomprise an analog switch 91 (such as, for example, ADG736), anamplifier 92 (such as INA333), various fixed and/or variable attenuatorsand wires as shown in the figure, etc., commonly found in electricalcircuits. The exemplary circuit 90 shown in FIG. 1C has wiringconsistent with the exemplary device 100 shown in FIG. 1B, in that wire25A provides current to both excitation electrode 25 and thermistor 102,and wire 102A transmits temperature data from thermistor 102. Anexemplary circuit 90 of the present application is not limited to thespecific circuit 90 shown in FIG. 1C, which is provided as at least oneexample of how the various electrodes, wires, and thermistor 102 connectwithin an exemplary device 100/system 200.

Another exemplary embodiment of at least part of an exemplary device 100of the present disclosure is shown in FIG. 1B. As shown in FIG. 1B,device 100 comprises the same/similar arrangement of electrodes 25, 26,27, and 28 and corresponding wires 25A, 26A, 27A, and 28A as shown inFIG. 1B, but also includes a thermistor electrode 102C positioned nearthermistor 102 along device 100. Thermistor electrode 102C, in at leastone embodiment, may couple to wire 25A and 102A to provide current tothermistor 102 and provide temperature data from thermistor 102,respectively.

In at least one embodiment, thermistor 102 is positioned along elongatedbody 102 proximal to detector 204. When positioned in this arrangement,for example, thermistor 102 may operate to detect temperature of aninjected fluid prior to detector 204 obtaining conductance data of thesame injected fluid. Thermistor 102, in both embodiments, may bepositioned distal to detector 204 or physically within detector 204. Anexemplary thermistor 102 of the present disclosure is capable ofdetecting fluid native to a luminal organ as well as fluid injected intothe luminal organ.

Thermistor 102, in an exemplary embodiment, may provide temperature datato a user by measuring temperature at the vicinity of thermistor 102,including, but not limited to, measuring temperature of a fluid presentwithin a luminal organ at or near thermistor 102. As referenced herein,a luminal organ may include, but is not limited to, various bodilylumens and vessels, including blood vessels (such as coronary arteries,carotid, femoral, renal and iliac arteries), an aorta, a biliary tract,a gastrointestinal tract, a urethra, a ureter, and an esophagus.

A device 100 of the present disclosure comprising a thermistor 102 wouldallow thermistor 102, when positioned proximal to the various electrodesreferenced herein, to detect a saline injection at the site of detector204. For example, an exemplary thermistor 102 of the present disclosurecould detect a saline injection at room temperature (approximately 20°C.) relative to body temperature (approximately 37-38° C.),

An exemplary embodiment of a system 200 obtaining parallel tissueconductance, measuring luminal cross-sectional areas, measuring fluidvelocity, and/or determining plague vulnerability using temperature ofthe present disclosure is shown in FIG. 2A. As shown in FIG, 2A, anexemplary system 200 comprises an exemplary device 100 of the presentdisclosure operatively coupled to a console 250 for controlling theoperation of the various components of device 100. Device 100, as shownin FIG. 2A, has two reference arrows, one pointing to the enlarged viewof the distal end of device 100, and another pointing to a portion ofdevice 100 that is not enlarged. These two reference arrows are notpointing to different portions of an exemplary system 200, but insteadare pointing to different portions of device 100.

Device 100, in at least one embodiment, may itself comprise a catheterhaving components as referenced above, whereby device 100 may bepositioned within an engagement catheter 260 which has, for example,been inserted into a luminal organ of a patient. In another exemplaryembodiment, device 100 comprises a wire having, for example, excitationelectrodes 25, 27, detection electrodes 26, 28, and a thermistor 102coupled thereto, whereby device 100 is positioned within engagementcatheter 260 for use within a patient's body.

As shown in FIG. 2A, an exemplary system 200 of the present disclosuremay comprise a number of connections to couple the various portions toone another. For example, and as shown in FIG. 2, console 250 may becoupled to device 100 by way of an extension cable 252 and a coupler254. In at least another embodiment, device 100 may be coupled directlyto console 250 without the use of an extension cable 252 or a coupler254. An exemplary system 200 may also comprise an injector 256 (anexemplary solution source such as a syringe, for example) connected toengagement catheter 260 either directly via adaptor 262 or by way of aninjector tube 264 positioned between injector 256 and adaptor 262.Injector 256, in at least another embodiment, may be coupled directly tothe lumen of an exemplary device 100 so that the solution may beinjected therethrough and through a auction/infusion port 35, 36, 37 (asdescribed in. FIGS. 2B-2G below) and into a luminal organ.

Console 250, in at least one exemplary embodiment and as shown in FIG.2A, may comprise a thermistor excitation device 270 for theexcitation/operation of thermistor 102, and an amplifier 272 foramplifying a temperature signal from thermistor 102. Console 250 mayfurther comprise an analog signal conditioning device 274 for filteringthe amplified temperature signal from amplifier 272, and a converter 276(an analog-to-digital converter spare channel, for example) forconverting the temperature signal as needed. Thermistor excitationdevice 270, amplifier 272, analog signal conditioning device 274, andconverter 276 may be positioned upon, for example, circuit board 278positioned within console 250, and/or each of said components may becoupled directly or indirectly to a ground 280.

System 200 may also comprise one or more components relating to theexcitation of detector 204 and obtaining conductance signals therefrom.For example, system 200 may comprise a stimulator 218 (an exemplarycurrent source) to provide a current to excite detection device 100and/or facilitate operation of thermistor 102 (similar to a thermistorexcitation device 270), and a data acquisition and processing system 220capable of receiving conductance data from detector 204 and to processthe conductance data. In at least one embodiment, data acquisition andprocessing system 220 is further capable of calculating a paralleltissue conductance based in part upon conductance data and a knownconductivity of a solution injected into a luminal organ at or neardetection electrodes 26, 28 (of, for example, detector 204). In at leastanother embodiment, data acquisition and processing system 220 iscapable of calculating a cross-sectional area of a luminal organ basedin part upon the conductance data and a known conductivity of a of asolution injected into a luminal organ at or near detection electrodes26, 28 (of, for example, detector 204). Furthermore, an exemplary system200 may also comprise a computer 228 for additional data processing asdesired. Computer 228, in at least one embodiment, comprises a displayfor displaying conductance and/or temperature data, for example. In atleast another embodiment, data acquisition and processing system 220 anda computer 228 are the same device, and each may perform the function ofthe other as referenced herein. Such a system 200 may also optionallycontain signal conditioning equipment for recording of fluid flow withina luminal organ. In at least one embodiment, the impedance and pressuredata are analog signals may be converted by analog-to-digital converters230 and transmitted to computer 228 for on-line display, on-lineanalysis and storage. In another embodiment, all data handling is doneon an entirely analog basis. Various systems 200 of the presentdisclosure may comprise any number of devices 100 referenced hereinhaving one or more features and/or components as referenced herein inconnection with said exemplary devices 100.

In addition, an exemplary detection device 100 of the present disclosuremay comprise any number of devices 100 as shown in. FIGS. 2B-2G.Referring to FIGS. 2B, 2C, 2D, and 2E, several exemplary embodiments ofthe detection devices 100 are illustrated. The detection devices 100shown contain, to a varying degree, different electrodes, thermistors102, and number and optional balloon(s). With reference to theembodiment shown in FIG. 2B, there is shown an impedance catheter 20 (anexemplary detection device 100) with four electrodes 25, 26, 27 and 28placed close to the tip 19 of the catheter 20. A thermistor 102 ispositioned proximal to electrodes 25, 26, 27, 28 to detect temperatureof a fluid present in a luminal organ as referenced herein. Proximal tothese electrodes is an angiography or stenting balloon 30 capable ofbeing used for treating stenosis. Electrodes 25 and 27 are excitationelectrodes, while electrodes 26 and 28 are detection electrodes, whichallow measurement of cross-sectional area using detection device 100, asdescribed in further detail herein. The portion of catheter 20 withinballoon 30 includes an infusion port 35 and a pressure port 36.

Catheter 20 may also advantageously include several miniature pressuretransducers 48 (as shown in FIG. 2B) carried by catheter 20 or pressureports 36 for determining the pressure gradient proximal at the sitewhere the CSA is measured. The pressure may be measured inside theballoon 30 and proximal, distal to and at the location of thecross-sectional area measurement, and locations proximal and distalthereto, thereby enabling the measurement of pressure recordings at thesite of stenosis and also the measurement of pressure-difference alongor near the stenosis. In at least one embodiment, and as shown in FIG.2B, catheter 20 includes pressure port 90 and pressure port 91 proximalto or at the site of the cross-sectional measurement for evaluation ofpressure gradients. As described below with reference to FIGS. 2H, 2I,and 2J, and in at least one embodiment, pressure ports 90, 91 areconnected by respective conduits in catheter 20 to pressure sensorswithin system 200. Such pressure sensors are well known in the art andinclude, for example, fiber-optic systems, miniature strain gauges, andperfused low-compliance manometry.

In at least one embodiment, a fluid-filled silastic pressure-monitoringcatheter is connected to a pressure transducer 48. Luminal pressure canbe monitored by a low compliance external pressure transducer 48 coupledto the infusion channel of the catheter. Pressure transducer 48calibration may be carried out by applying 0 and 100 mmHg of pressure bymeans of a hydrostatic column, for example.

In an exemplary embodiment, and shown in FIG. 2C, catheter 39 includesanother set of excitation electrodes 40, 41 and detection electrodes 42,43 located inside the angioplastic or stenting balloon 30 for accuratedetermination of the balloon 30 cross-sectional area during angioplastyor stent deployment. These electrodes are to addition to electrodes 25,26, 27 and 28 and are in addition to thermistor 102.

In another exemplary embodiment, and as shown in FIG. 2G, severalcross-sectional areas can be measured using an array of 5 or moreelectrodes. Here, the excitation electrodes 51, 52, are used to generatethe current while detection electrodes 53, 54, 55, 56 and 57 are used todetect the current at their respective sites. A thermistor 102, as shownin FIG. 2G, is also present along device 100 proximal to saidelectrodes.

The tip of an exemplary catheter can be straight, curved or with anangle to facilitate insertion into the coronary arteries or otherlumens, such as, for example, the biliary tract. The distance betweenthe balloon 30 and the electrodes is usually small, in the 0.5-2 cmrange, but can be closer or further away, depending on the particularapplication or treatment involved.

In at least another embodiment, and shown in FIG. 2D, catheter 21 hasone or more imaging or recording device, such as, for example,ultrasound transducers 50 for cross-sectional area and wall thicknessmeasurements. As shown in this exemplary embodiment, transducers 50 arelocated near the distal tip 19 of catheter 21.

FIG. 2E shows an exemplary embodiment of an impedance catheter 22without an angioplastic or stenting balloon 30. This catheter 22 alsocomprises an infusion or injection port 35 located proximal relative tothe excitation electrode 25 and pressure port 36.

With reference to the exemplary embodiment shown in FIG. 2F, electrodes25, 26, 27, 28 can also be built onto a wire 18, such as, for example, apressure wire, and inserted through a guide catheter 23 where theinfusion of bolus can be made through the lumen of the guide catheter37. A thermistor 102, as shown FIG. 2F, can also be built onto wire 18and be used to detect fluid temperatures.

With reference to the embodiments shown in FIGS. 2B-2G, the impedancecatheter advantageously includes optional ports 35, 36, 37 for suctionof contents of the organ or infusion of fluid. Suction/infusion ports35, 36, 37 can be placed as shown with the balloon 30 or elsewhere bothproximal or distal to the balloon 30 on the various catheters. The fluidinside the balloon 30 may be any biologically compatible conductingfluid. The fluid to inject through the infusion port or ports can be anybiologically compatible fluid but the conductivity of the fluid isselected to be different from that of blood (e.g., saline).

In at least another embodiment (not illustrated), an exemplary cathetercontains an extra channel for insertion of a guide wire to stiffen theflexible catheter during the insertion or data recording. In yet anotherembodiment (not illustrated), the catheter includes a sensor formeasurement of the flow of fluid in the body organ.

As described below with reference to FIGS. 2H, 2I, and 2J, theexcitation and detection electrodes are electrically connected toelectrically conductive leads in the catheter for connecting theelectrodes to the stimulator 218, for example.

FIGS. 2H and 2I illustrate two exemplary embodiments 20A and 20B of thecatheter in cross-section. Each embodiment has a lumen 60 for inflatingand deflating a balloon 30 and a lumen 61 for suction and infusion, Thesizes of these lumens can vary in size. The impedance electrodeelectrical leads 70A are embedded in the material of the catheter in theembodiment in FIG. 2H, whereas the electrode electrical leads 70B aretunneled through a lumen 71 formed within the body of catheter 70B inFIG. 2I. In this exemplary embodiment, thermistor lead 75A is shown inFIG. 2H as being embedded within the catheter material, whereasthermistor lead 75B is shown as being tunneled through lumen 71 ofcatheter 70B.

Pressure conduits for perfusion manometry connect the pressure ports 90,91 to transducers included in system 200. As shown in FIG. 2H, pressureconduits 95A may be formed in 20A. In another exemplary embodiment,shown in FIG. 2I, pressure conduits 95B constitute individual conduitswithin a tunnel 96 formed in catheter 20B. In the embodiment describedabove where miniature pressure transducers 48 are carried by thecatheter, electrical conductors will be substituted for these pressureconduits.

At least a portion of an exemplary system 200 for obtaining a paralleltissue conductance within a luminal organ of the present disclosure isshown in FIG. 2J. As shown in FIG. 2J, an exemplary system 200 of thepresent disclosure comprises a detection device 100 operably connectedto a manual or automatic system 222 for distension of a balloon 30 andto a system 224 for infusion of fluid or suction of blood. In addition,and as shown in FIG. 2J, system 200 may comprise a stimulator 218 toprovide a current to excite detection device 202, and a data acquisitionand processing system 220 to process conductance data. Furthermore, anexemplary system 200 may also comprise a signal amplifier/conditioner(not shown) and a computer 228 for additional data processing asdesired. Such a system 200 may also optionally contain signalconditioning equipment for recording of fluid flow in the luminal organ.

At least a portion of another exemplary embodiment of a device 100 forobtaining parallel tissue conductance, measuring luminal cross-sectionalareas, measuring fluid velocity, and/or determining plaque vulnerabilityusing temperature of the present disclosure is shown in FIG. 2K. Asshown in FIG. 2K, an exemplary device 100 comprises a thermistor 102coupled thereto, whereby thermistor 102 is connected to, for example,console 250 (as shown in FIG. 2) by way of thermistor wires 102A and102B. Thermistor wires 102A and 102B may be coupled to console 250, asreferenced above, or to any number of other components of an exemplarydevice 100/system 200 of the present disclosure so that thermistor 102may operate and/or provide data to user in accordance with the presentdisclosure. In at least one embodiment, thermistor wire 102A providescurrent to thermistor 102 to facilitate its operation, while thermistorwire 102B carries temperature data from thermistor 102. Any number ofadditional components and/or features of other devices 100 of thepresent disclosure may also be part of such an exemplary embodiment of asuch a device 100. Thermistor 102 is shown in an enlarged view in FIG.2K noting that, for example, device 100 may comprise any number ofcatheters or wires with the components referenced herein, including, butnot limited to, pressure wires, guide wires, or guide catheters.Thermistor 102, in at least one embodiment, is positioned along anelongated body 202 of device 100, wherein elongated body 202 has alongitudinal axis, a proximal end (further from thermistor 102), and adistal end (closer to thermistor 102). In addition, and as shown in FIG.2K, device 100 may also comprise a thermistor electrode 102C asdescribed herein.

In an exemplary embodiment of a device 100 of the present disclosure,device 100 may further comprise a data acquisition and processing system220 capable of receiving temperature data from thermistor 102. In atleast one embodiment, data acquisition and processing system 220 isfurther capable of determining vulnerability of a plaque within aluminal organ based in part from the temperature data from thermistor102. Such an exemplary embodiment of device 100, as referenced above,may comprise any number of other components and/or features asreferenced herein in connection with various other device 100embodiments.

In an exemplary embodiment, a system 200 is pre-calibrated and adetection device 100 is available in a package. In such an embodiment,for example, the package may also contains sterile syringes (injectors256) with the fluid(s) to be injected. The parallel conductance,cross-sectional area, plaque vulnerability, and other relevant measuressuch as distensibility, tension, etc., may then typically appear on thedisplay of computer 228. In such an embodiment, the user can then removethe stenosis by distension or by placement of a stent.

An exemplary device 100 of the present disclosure that can sense thepresence of saline will have a number of advantages to make existingtechnologies relating to the sizing of vessels, determination offractional flow reserves (FFRs), and plaque vulnerability determinationsmore reliable and robust.

Steps of an exemplary method to obtain parallel tissue conductance,measure luminal cross-sectional areas, measure fluid velocity, and/ordetermine plaque vulnerability using temperature within a luminal organof the present disclosure are shown in FIG. 3A. As shown in FIG. 3A, anexemplary method 300 comprises the step of introducing at least part ofa detection device 100 into a luminal organ at a first location(introduction step 302), whereby, in at least one embodiment, detectiondevice 100 comprises a detector 204 and a thermistor 102 positionedrelative to the detector 204. Method 300 may further comprise the stepof applying current to detection device 100 to allow detector 204 tooperate (current application step 304). The application/excitation ofcurrent may be performed using a stimulator 218. Method 300, in at leastone embodiment, further comprises the steps of obtaining a firsttemperature measurement of a fluid native to the first location, suchas, for example, blood within a blood vessel (temperature measurementstep 306), and injecting a solution having a known conductivity into theluminal organ at or near detector 204 of detection device 100 (solutioninjection step 308).

After injection of the solution, an exemplary method 300 furthercomprises the steps of detecting a temperature change at the firstlocation indicative of the injected solution (temperature changedetection step 310), and measuring an output conductance in connectionwith the injected solution based upon the detected temperature change(conductance measurement step 312). Such an exemplary method 300 maythen further comprise the step of calculating a parallel tissueconductance at the first location (calculation step 314), in anexemplary embodiment, based in part upon the output conductance and theconductivity of the injected solution. Calculation step 314, in at leastone embodiment, may comprise the optional step of calculating across-sectional area of the luminal organ at the first location.

In at least one exemplary method 300 of the present disclosure, method300 further comprises the optional steps of selecting anappropriately-sized stent 160 (as shown in FIG. 5B, for example) basedon the cross-sectional area at the first location (stent selection step316), and implanting stent 160 into the luminal organ at or near thefirst location (a first version of a stent implantation step 318). Inanother exemplary embodiment, method 300 comprises the optional step ofselecting a balloon catheter to be introduced into the luminal organbased upon the cross-sectional area of the luminal organ at the firstlocation (a first version of catheter selection step 320).

As used within the various methods 300 of the present disclosure,detector 204 of device 100 may comprise two detection electrodespositioned in between two excitation electrodes, wherein the twoexcitation electrodes are capable of producing an electrical field. Inan exemplary conductance measurement step 312, for example, conductancemeasurement step 312 is performed using the detection device 100.

In at least one exemplary method 300 of the present disclosure,temperature measurement step 306 is performed using the thermistor. Inan exemplary embodiment, the fluid native to the first locationcomprises blood, and wherein the injected solution comprises saline. Inanother exemplary method 300, temperature measurement step 306 comprisesobtaining multiple temperature measurements of the fluid native to thefirst location over time and displaying the multiple temperaturemeasurements on a display (computer 228). In an additional method 300,temperature change detection step 310 comprises obtaining additionaltemperature measurements and displaying the additional temperaturemeasurements on the display (computer 228).

In an exemplary method 300 of the present disclosure, method 300 furthercomprises the optional step of obtaining a native conductance inconnection with the native fluid prior to the step of injecting asolution (native conductance measurement step 322). In such a method300, for example, native conductance measurement step 322 may compriseobtaining multiple native conductances, and conductance measurement step312 may comprise obtaining multiple output conductances. In at least oneembodiment, the multiple native conductances and the multiple outputconductances are displayed on a display (computer 228). As shown in FIG.3A, optional native conductance measurement step 322 may be performeddirectly after current application step 304, for example, or may beperformed before or after any party number of the steps referencedwithin FIG. 3A.

Detecting temperature change, as referenced above, may be indicative ofthe presence of an injected solution at the location of, for example,thermistor 102 when device 100 is positioned within a luminal organ. Inat least one embodiment, such a temperature change may be at least 5° C.lower than the first temperature measure. In an exemplary embodiment ofa method 300 of the present disclosure, solution injection step 308temporarily substantially displaces the blood at the first location.Furthermore, and in at least one embodiment, conductance measurementstep 312 may include measuring multiple output conductances until thetemperature within the luminal organ reaches a threshold temperature. Inat least one embodiment, the threshold temperature is within about 2° C.of the first/native temperature measurement, and in other embodiments,the threshold temperature could be any number of temperatures includingand between the lowest and highest detected temperatures.

In at least one embodiment, an optimal output conductance is obtained byaveraging the multiple output conductances. In another embodiment, theoutput conductance having a largest or smallest value within themultiple output conductances is deemed an optimal output conductance. Asshown above, a user has many options for determining which conductancevalues to use, as those conductance values obtained between the time ofdetecting a temperature change and the threshold temperature would beindicative of a successful saline injection.

An exemplary detection device 100 used in connection with an exemplarymethod 300 of the present disclosure may further comprise an inflatableballoon 30 along a longitudinal axis of the detection device 100. Withsuch a device 100, for example, method 300 may further comprise theoptional step of inflating balloon 30 to breakup materials causingstenosis at the first location (a first version of a balloon inflationstep 324). Furthermore, and in at least one embodiment, detection 100may further comprise a stent 160 (as shown in FIG. 5B, for example),located over the balloon 30, wherein stent 160 is capable of beingdistended to a desired lumen size and implanted into the luminal organat or near the first location. With such a device 100, for example,method 300 may further comprise the optional steps of distending stent160 by inflating balloon 30 (another version of balloon inflation step324), and releasing and implanting stent 160 into the luminal organ ator near the first location (a second version of a stent implantationstep 318). As referenced above, the various method steps may beperformed in the order as shown in FIG. 3A, but are not limited to beingperformed in such an order. For example, when positioning a stent 160,stent implantation step 318 may be performed without balloon inflationstep 324 or may be performed after balloon inflation step 324.

In at least an additional embodiment of a method 300 of the presentdisclosure, detection device 100 further comprises a pressure transducer48 (as shown in FIG. 2B). Using such a device 100, for example, method300 may further comprise the optional steps of measuring a firstpressure gradient value from the pressure transducer at or near thefirst location (pressure gradient measurement step 326) and calculatinga cross-sectional area of the treatment site based in part on theparallel tissue conductance and the first pressure gradient value(calculation step 314).

In at least another embodiment of a method 300 of the presentdisclosure, method 300 father comprises the optional step of calculatinga first nodal voltage and a first electrical field based on the outconductance and a first current density (first nodal voltage calculationstep 328). In such an embodiment, method 300 may further comprise theoptional steps of applying finite element analysis to the first nodalvoltage and first electrical field values (finite element analysisapplication step 330), determining appropriate catheter dimensions forminimizing nonparallel electrical field lines at the first location(catheter dimension determination step 332), and selecting anappropriately-sized catheter for introduction into the luminal organ ator near the first location (a second version of catheter selection step320). In at least one embodiment, finite element analysis applicationstep 330 is performed using a finite element software package.

In at least another exemplary method 300 of the present disclosure, andas shown in FIG. 3B, method 310 comprises introduction step 302, currentapplication step 304, native conductance measurement step 322,temperature measurement step 306, solution injection step 308,temperature change detection step 310, conductance measurement step 312,and calculation step 314. In at least one embodiment, calculation step314 comprises the optional step of calculating a cross-sectional area ofthe luminal organ at the first location.

In yet another exemplary method 300 of the present disclosure, and asshown in FIG. 3C, method 300 comprises introduction step 302, currentapplication step 304, temperature measurement step 306, solutioninjection step 308, temperature change detection step 310, conductancemeasurement step 312, and calculation step 314, wherein calculation stepcomprises calculating a cross-sectional area of the luminal organ at thefirst location based in part upon the output conductance and theconductivity of the injected solution. Such a method 300, in at leastone embodiment, may further comprise the optional step of selecting aballoon catheter to be introduced into the luminal organ based upon thecross-sectional area of the luminal organ at the first location (a firstversion of catheter selection step 320).

Steps of another exemplary method 300 to obtain parallel tissueconductance, measure luminal cross-sectional areas, measure fluidvelocity, and/or determine plaque vulnerability using temperature withina luminal organ of the present disclosure are shown in FIG. 4A. As shownin FIG. 4A, an exemplary method 300 comprises the steps of introducingat least part of a detection device into a luminal organ at a plaquesite, the detection device having a thermistor (a version ofintroduction step 302), injecting a solution into the luminal organ ator near the thermistor of the detection device (a version of solutioninjection step 308), and detecting a first temperature measurement atthe plaque site indicative of a plaque and the injected solution (aversion of temperature measurement step 306). Such an exemplary method300 may further comprise the step of determining vulnerability of aplaque at the plaque site based in part upon the first temperature atthe plaque site (plaque vulnerability determination step 400).

In at least one exemplary embodiment, temperature measurement step 306is performed using the thermistor. In another exemplary embodiment ofmethod 300, the injected solution comprises saline. In at least anotherexemplary embodiment of a method 300 of the present disclosure,temperature measurement step 306 comprises detecting multipletemperature measurements at the plaque site over time and displaying themultiple temperature measurements on a display.

In an exemplary method 300 of the present disclosure, and as shown inFIG. 4A, method 300 comprises the optional steps of moving the detectiondevice within the luminal organ to a plaque-free location (devicemovement step 402), injecting additional solution into the luminal organat or near the thermistor of the detection device (additional solutioninjection step 404), and detecting a second temperature measurement atthe plaque-free location indicative of the injected solution (secondtemperature detection step 406).

In at least one embodiment of a plaque vulnerability determination step400 of an exemplary method 300 of the present disclosure, plaquevulnerability determination step 400 is further based upon a differencebetween the first temperature measurement and the second temperaturemeasurement. In such an embodiment, a plaque may be determined to beless vulnerable of the difference between the first temperaturemeasurement and the second temperature measurement is zero to relativelylow, and the plaque may be determined to be more vulnerable of thedifference between the first temperature measurement and the secondtemperature measurement is relatively high. In at least one embodiment,the plaque may be determined to be vulnerable if the difference betweenthe first temperature measurement and the second temperature measurementis about 1° C. Any number of additional steps of an exemplary method 300of the present disclosure may also apply to the method 300 shown in FIG.4A, as well as any other depiction of an exemplary method 300 of thepresent disclosure.

In at least another method 300 of the present disclosure, and as shownin FIG. 4B, method 300 comprises introduction step 302, solutioninjection step 308, temperature measurement step 306, device movementstep 402, additional solution injection step 404, a second temperaturemeasurement step 306, and the step of determining vulnerability of aplaque based upon a difference between a first temperature measurementand a second temperature measurement (a version of plaque vulnerabilitydetermination step 400). Using such a method 300, for example, devicemovement step 402 may be to move the device 100 from a plaque site to aplaque-free site, or may be to move the device 100 from a plaque-freesite to a plaque site.

In at least one embodiment, the two temperature measurement steps 306are performed using a thermistor 102. In at least another embodiment,the first temperature measurement step 306 comprises detecting multipletemperature measurements at the first location over time, and the secondtemperature measurement step 306 comprises detecting multipletemperature measurements at the second location over time and displayingthe multiple temperature measurements on a display. In at least oneexemplary embodiment of a method 300 of the present disclosure, thefirst temperature measurement and the second temperature measure (fromthe two temperature measurement steps 306) are further indicative ofluminal organ tissue.

Referring to the embodiment of an exemplary device 100 of the presentdisclosure shown in FIG. 5A, the angioplasty balloon 30 is selected onthe basis of G_(p) (and/or a direct cross-sectional area determination,for example) and is shown distended within a coronary artery 150 for thetreatment of stenosis. As described above with reference to FIG. 2C, aset of excitation electrodes 40, 41 and a set of detection electrodes42, 43 are located within the angioplasty balloon 30. In anotherembodiment, and as shown in FIG. 5B, an angioplasty balloon 30 is usedto distend a stent 160 within blood vessel 150. As shown in FIGS. 5A and5B, such exemplary devices 100 comprise a thermistor 102 coupled theretoas referenced herein in connection with various other device 100embodiments, whereby thermistor 102 is operable to detect fluidtemperatures as referenced herein.

CSA and Gp

A two injection method allowing for the simultaneous determination ofcross-sectional area (CSA) and parallel conductance (G_(p)) of luminalorgans are currently known in the art by way of U.S. Pat. No. 7,454,244to Kassab. As referenced therein, each injection provides a knownconductivity-conductance (σ-G) relation or equation as per an Ohm's lawmodification that accounts for parallel conductance (namely currentlosses from the lumen of vessel):

G=(CSA/L)σ+G _(p)   [1]

wherein G is the total conductance, CSA is the cross-sectional area ofthe luminal organ (which may include, but is not limited to, variousbodily lumens and vessels, including blood vessels, a biliary tract, aurethra, and an esophagus, for example), L is a constant for the lengthof spacing between detection electrodes of the detection device used, σis the specific electrical conductivity of the fluid, and G_(p) is theparallel conductance (namely the effective conductance of the structureoutside of the fluid).

The physical principle for sizing of vessel is based on an Ohm-type lawwhich uses saline to calibrate the vessel size relative to known phantomdimensions. The issue arises as to when a system 200 of the presentdisclosure can sense the presence of saline in order to measure thesaline conductance whose conductivity is known (unlike blood, whoseconductivity is not precisely known and varies in different patients andunder different conditions based upon, for example, hematocrit, shearrate, and blood cell orientation). The conductance of saline may deflectup, down or remain the same depending on weather it is more conductive,less conductive or of same conductivity as that of blood. Since this mayvary in different patients depending on their blood properties,composition, etc., it is beneficial to have an independent sensor todenote the presence of saline.

Equation [1], and derivations and/or related equations theretocomprising CSA and Gp, are both temperature dependent as they arefunctions of conductance and conductivity. Each 1° C. change intemperature can cause a 1% change in conductance or conductivity. Forexample, if a user of a device 100/system 200 of the present disclosurebelieve that conductance measurements are being made within a body at37° C., but such measurements are actually being made at 27° C. due tothe louver temperature of a saline injection, for example, thoseconductance measurements could be incorrect by approximately 10% ormore. If those incorrect measurements are then used to determine anappropriately-sized stent, such a stent could either be too large or toosmall for that particular vessel.

By knowing the temperature at the time/location of injection, one canthen determine the linear relationship between conductivity andtemperature. For example, and as referenced herein, using a device100/system 200 of the present disclosure would allow a user to know thetemperature of the injected bolus at the time the conductancemeasurements are taken, as a thermistor 102 can provide one or moretemperature measurements to the user before, during, and/or after thebolus injection itself.

Calibration of such a device 100/system 200, for example, may be madeusing phantoms (tubes with known diameters) are referenced herein. Toobtain a known calibration range, one could use a device 100/system 200of the present disclosure to “size” the phantom, for example, at variousincrements between 20° C. and 40′C. For example, a phantom could beplaced within a 0.9% saline (normal) or 0.45% saline (half-normal) bathat 20° C., and device 100 could be used to obtain conductancemeasurements. The bath could then be warmed to 22° C., for example, andadditional measurements could be obtained, Additional measurements at24° C., 26° C., etc., up to 40° C. could be made, and that calibrationdata could be programmed into system 200, for example, so that the mostaccurate conductance measurements could then be made within a vessel ofan unknown diameter, such as within a mammalian bodily vessel/luminalorgan. Therefore, when a user knows the bolus temperature, the user canmatch conductivity to temperature to obtain the most accurate readings.

Automation of Sizing and Fluid Velocity Measurements

FIG. 6 shows a graph demonstrating the use of an exemplary device100/system 200 of the present disclosure. Two data lines are shown inFIG. 6, namely an upper line representing the conductivity of fluiddetected by a detector 204 of a device 100 of the present disclosureover time, and a lower line representing temperature over time asdetected by a thermistor 102 of a device 100 of the present disclosure.As shown in FIG. 6, the upper line remains relatively constant overtime, and then deflects upwards for a period of time, eventually fallingback to its original constant level. This upward deflection isindicative of the detection of saline that is more conductive than aparticular patient's blood, resulting in a temporary upward deflectionat the time the saline is detected by device 100. In this instance, thetemperature (lower line) shows a clear downward deflection, a slightplateau, and is followed by recovery of temperature when the bloodwashes out the saline. The plateau represents unmixed saline and henceconductance measurement at this instant of time is preferred.

The beginning of such a measurement, for example, can be triggered by athreshold drop in temperature such as a 5° C. drop relative to thebaseline temperature. The end of measurement (to define an interval forpreferred detection) can be triggered by the recovery of the detected.temperature to the baseline, such as within 2° C. of the baseline.Within this interval, the conductance measurement (used for sizing,fractional flow reserve, plaque vulnerability and/or plaque-typedetermination, etc.) can be made at the minimum plateau of temperature.

For a fluid velocity determination, for example, one may lookimmediately to the right of first trigger to obtain the conductance-timedeflection curve. If the thresholds are not realized, due to a badinjection (when the catheter not engaged into the artery) or substantialmixing saline and blood (from too slow of an injection), no measurementwill be provided by the device 100/system 200 and the operator can thenrepeat the injection in attempt to obtain a suitable measurement.

Consistent with the foregoing, steps of an exemplary method 300 toobtain parallel tissue conductance, measure luminal cross-sectionalareas, measure fluid velocity, and/or determine plaque vulnerabilityusing temperature within a luminal organ of the present disclosure shownin FIG. 7. As shown in FIG. 7, an exemplary method 300 comprisesintroducing at least part of a detection device into a luminal organ ata first location wherein the detection device has a thermistor (aversion of introduction step 302), obtaining a first temperaturemeasurement indicative of a fluid native to the first location (aversion of temperature measurement step 306), injecting a solution intothe luminal organ at a known distance from the thermistor of thedetection device (a version of solution injection step 308), anddetecting a temperature change at the first location indicative of theinjected solution (a version of temperature change detection step 310).Such an exemplary method 300 may also comprise the steps of calculatingthe time from injecting the solution to detecting the temperature changeat the first location (time calculation step 700), and calculating fluidvelocity at the first location based in part upon calculated time andthe known distance from the injection to the thermistor (fluid velocitycalculation step 702). As referenced herein, any number of other method300 steps, as well as any number of devices 100 and/or systems 200 ofthe present disclosure may be used in connection with the aforementionedexemplary method 300.

The integrity of the injection can also be assessed, with feedbackprovided to the operator/physician. The degree of deflection, in atleast one embodiment, can be used to make this assessment. For example,an injection made at 20° C. (room temperature) through the catheter isexpected to increase in temperature (heat up) by couple of degrees atthe site of coronary artery. Hence, a deflection to 25° C., for example,can be used to accept the measurement. If the deflection is only to 30°C., which is still large enough to trigger the measurement, themeasurement will be rejected and the operator may then decide to repeatthe injection. Therefore, a visual display of the temperature changesalong with system 200 instructions to the user would help ensure theintegrity of the injections and the corresponding output measurements.It is noted that conductance measurements triggered by temperature willdetect upward deflection, downward deflection, or no deflectionregardless of the relative conductance of saline to blood.

Since the conductivity values for saline are temperature-dependent (forexample, an 0.5-1.0° C. increase in temperature resulting in a higherconductivity), an accurate determination temperature will allow thecorrect values of conductivities to be used given that a linear relationexists between temperature and conductivity. This will provide a moreaccurate measurement of CSA given its direct relation with conductivity.The linear relation between conductivity and temperature will allow anexemplary system 200 of the present disclosure to assign the correctconductivity depending on the recorded temperature of saline at the siteof measurement.

Detection of Vulnerable Plaque

It is known that a vulnerable plaque that may be susceptible to ruptureis an active inflammation with a locally higher temperature (e.g.,within a degree higher than surrounding tissue/blood). Previous attemptsmade at measuring the temperature of a lesion to determine vulnerabilityhave encountered the following difficulty. A plaque (even intermediatedisease or stenosis) can produce local flow disturbances which can leadto viscous dissipation due to viscosity of blood. The energy dissipationtranslates into thermal heat (i.e., a slight increase in temperature,within 1° C.) in the vicinity of the stenotic lesion. Hence, a rise intemperature in the vicinity of lesion may be due to the flow disturbanceenergy dissipation regardless of plaque temperature.

To correct for this potential incorrect determination, the disclosure ofthe present application discloses the measurement of temperature using athe thermistor 102 positioned along a device 100 of the presentdisclosure at the plaque site during the saline injection, as opposed toan attempted temperature measurement in the presence of blood as withprevious attempts. The rationale is that saline has approximately onefourth the viscosity of blood and therefore will lead to far lessviscous dissipation (roughly one fourth) which can prevent the “noise”of previous measurements. This will allow the present system to detectlargely the temperature of the lesion as opposed to nearby hemodynamicdisturbances during the saline injection.

To consider a method of measuring parallel conductance (G_(p)) relatedimpedance, which are used to determine CSA or evaluate the type and/orcomposition of a plaque, a number of approaches may be used. In oneapproach, luminal cross-sectional area is measured by introducing acatheter from an exteriorly accessible opening (e.g., mouth, nose oranus for GI applications; or e.g., mouth or nose for airwayapplications) into the hollow system or targeted luminal organ. In anexemplary approach, G_(p) is measured by introducing a catheter from anexteriorly accessible opening into the hollow system or targeted luminalorgan. For cardiovascular applications, the catheter can be insertedinto the organs in various ways, for example, similar to conventionalangioplasty. In at least one embodiment, an 18 gauge needle is insertedinto the femoral artery followed by an introducer, and a guide wire isthen inserted into the introducer and advanced into the lumen of thefemoral artery. A 4 or 5 Fr conductance catheter is then inserted intothe femoral artery via wire and the wire is subsequently retracted. Thecatheter tip containing the conductance (excitation) electrodes can thenbe advanced to the region of interest by use of x-ray (usingfluoroscopy, for example). In another approach, this methodology is usedon small to medium size vessels, such as femoral, coronary, carotid, andiliac arteries, for example.

With respect to the solution injection, studies indicate that aninfusion rate of approximately 1 ml/s for a five second interval issufficient to displace the blood volume and results in a local pressureincrease of less than 10 mmHg in the coronary artery. This pressurechange depends on the injection rate, which should be comparable to theorgan flow rate. In at least one approach, dextran, albumin or anotherlarge molecular weight molecule can be added to the solution (saline,for example) to maintain the colloid osmotic pressure of the solution toreduce or prevent fluid or ion exchange through the vessel wall.

In an exemplary approach, a sheath is inserted either through thefemoral or carotid artery in the direction of flow. To access the leftanterior descending (LAD) artery, the sheath is inserted through theascending aorta. For the carotid artery, where the diameter is typicallyon the order of 5.0-5.5 mm, a catheter having a diameter of 1.9 mm canbe used. For the femoral and coronary arteries, where the diameter istypically in the range from 3.5-4.0 mm, a catheter of about 0.8 mmdiameter would be appropriate. Such a device can be inserted into thefemoral, carotid or LAD artery through a sheath appropriate for theparticular treatment. Measurements for all three vessels can besimilarly made.

The saline solution can be injected by hand or by using a mechanicalinjector to momentarily displace the entire volume of blood or bodilyfluid in the vessel segment of interest. The pressure generated by theinjection will not only displace the blood in the antegrade direction(in the direction of blood flow) but also in the retrograde direction(momentarily push the Hood backwards). In other visceral organs that maybe normally collapsed, the saline solution will not displace blood as inthe vessels but will merely open the organs and create a flow of thefluid.

The injection described above may be repeated at least once to reduceerrors associated with the administration of the injection, such as, forexample, where the injection does not completely displace the blood orwhere there is significant mixing with blood. Bifurcation(s) (withbranching angle near 90 degrees) near the targeted luminal organ maypotentially cause an error in the calculated G_(p). Hence, generally thedetection device should be slightly retracted or advanced and themeasurement repeated. An additional application with multiple detectionelectrodes or a pull back or push forward during injection couldaccomplish the same goal. Here, an array of detection electrodes can beused to minimize or eliminate errors that would result from bifurcationsor branching in the measurement or treatment site.

In an exemplary approach, error due to the eccentric position of theelectrode or other imaging device can be reduced by inflation of aballoon on the device. The inflation of the balloon during measurementwill place the electrodes or other imaging device in the center of thevessel away from the wall. In the case of impedance electrodes, theinflation of the balloon can be synchronized with the injection of boluswhere the balloon inflation would immediately precede the bolusinjection.

CSAs calculated in connection with the foregoing correspond to the areaof the vessel or organ external to the device used (CSA of vessel minusCSA of the device). If the conductivity of the saline solution isdetermined by calibration with various tubes of known CSA, then thecalibration accounts for the dimension of the device and the calculatedCSA corresponds to that of the total vessel lumen as desired. In atleast one embodiment, the calibration of the CSA measurement system willbe performed at 37° C. by applying 100 mmHg in a solid polyphenolenoxideblock with holes of known CSA ranging from 7.065 mm² (3 mm in diameter)to 1017 mm² (36 mm in diameter). If the conductivity of the solution(s)is/are obtained from a conductivity meter independent of the device,however, then the CSA of the device is generally added to the computedCSA to give the desired total CSA of the luminal organ.

The signals obtained herein are generally non-stationary, nonlinear andstochastic. To deal with non-stationary stochastic functions, one mayuse a number of methods, such as the Spectrogram, the Wavelet'sanalysis, the Wigner-Ville distribution, the Evolutionary Spectrum,Modal analysis, or preferably the intrinsic model function (IMF) method.The mean or peak-to-peak values can be systematically determined by theaforementioned signal analysis and used to compute the G_(p) asreferenced herein.

In an exemplary approach for the esophagus or the urethra, theprocedures can conveniently be done by swallowing fluids of knownconductances into the esophagus and infusion of fluids of knownconductances into the urinary bladder followed by voiding the volume. Inanother approach, fluids can be swallowed or urine voided followed bymeasurement of the fluid conductances from samples of the fluid. Thelatter method can be applied to the ureter where a catheter can beadvanced up into the ureter rand fluids can either be injected from aproximal port on the probe (will also be applicable in the intestines)or urine production can be increased and samples taken distal in theureter during passage of the bolus or from the urinary bladder.

In another exemplary approach, concomitant with measuring thecross-sectional area and or pressure gradient at the treatment ormeasurement site, a mechanical stimulus is introduced by way ofinflating the balloon or by releasing a stent from the catheter, therebyfacilitating flow through the stenosed part of the organ. In anotherapproach, concomitant with measuring the cross-sectional area and orpressure gradient at the treatment site, one or more pharmaceuticalsubstances for diagnosis or treatment of stenosis is injected into thetreatment site. For example, in one approach, the injected substance canbe smooth muscle agonist or antagonist. In yet another approach,concomitant with measuring the cross-sectional area and or pressuregradient at the treatment site, an inflating fluid is released into thetreatment site for release of any stenosis or materials causing stenosisin the organ or treatment site.

Again, it is noted that the devices 100, systems 200, and methods 300described herein can be applied to any body lumen or treatment site. Forexample, the devices 100, systems 200, and methods 300 described hereincan be applied to any one of the following exemplary bodily holloworgans: the cardiovascular system including the heart, the digestivesystem, the respiratory system, the reproductive system, and theurogenital tract.

While various embodiments of devices and systems for obtaining paralleltissue conductance, measuring luminal cross-sectional areas, measuringfluid velocity, and/or determining plaque vulnerability usingtemperature and methods for using and performing the same have beendescribed in considerable detail herein, the embodiments are merelyoffered by way of non-limiting examples of the disclosure describedherein. It will therefore be understood that various changes andmodifications may be made, and equivalents may be substituted forelements thereof, without departing from the scope of the disclosure.Indeed, this disclosure is not intended to be exhaustive or to limit thescope of the disclosure.

Further, in describing representative embodiments, the disclosure mayhave presented a method and/or process as a particular sequence ofsteps. However, to the extent that the method or process does not relyon the particular order of steps set forth herein, the method or processshould not be limited to the particular sequence of steps described.Other sequences of steps may be possible. Therefore, the particularorder of the steps disclosed herein should not be construed aslimitations of the present disclosure. In addition, disclosure directedto a method and/or process should not be limited to the performance oftheir steps in the order written. Such sequences may be varied and stillremain within the scope of the present disclosure.

1. A method to obtain conductance data within a luminal organ, themethod comprising the steps of: operating a detection device having anelectrode and a thermistor, the detection device at least partiallypositioned within a luminal organ to detect a temperature change from afirst temperature to a temperature indicative of an injection of a bolusof a solution having a known conductivity; and obtaining multipleconductance measurements using the electrode of detection device priorto dilution of the bolus at least until a threshold temperature isreached.
 2. The method of claim 1, further comprising the step of:calculating a parallel tissue conductance at the first location based inpart upon the temperature change, at least one conductance measurementof the multiple conductance measurements, and the conductivity of theinjected solution.
 3. The method of claim 1, further comprising the stepof: calculating a dimension of the luminal organ based in part upon atleast one conductance measurement of the multiple conductancemeasurements.
 4. The method of claim 3, further comprising the steps of:selecting an appropriately-sized stent based upon the calculateddimension; and implanting the stent into the luminal organ.
 5. Themethod of claim 1, wherein the first temperature is a measurement ofblood obtained using the thermistor of the detection device.
 6. Themethod of claim 1, wherein the temperature change is based upon atemperature measurement at least 5° C. lower than the first temperature.7. The method of claim 1, wherein the threshold temperature is within 2°C. of the first temperature.
 8. The method of claim 1, furthercomprising the step of: calibrating the detection device using at leastone phantom immersed in a solution bath of the same solution injectedinto the luminal organ, wherein the solution within the solution bath isat a known temperature.
 9. The method of claim 1, wherein the detectiondevice further comprises an inflatable balloon along a longitudinal axisof the detection device.
 10. The method of claim 9, further comprisingthe step of: inflating the balloon to breakup materials causing astenosis within the luminal organ.
 11. The method of claim 9, whereinthe detection device further comprises a stent located over the balloon,the stent capable of being distended to a desired lumen size andimplanted into the luminal organ.
 12. A detection device configured toobtain conductance data within a luminal organ, comprising: an elongatedbody having a thermistor located thereon, the thermistor configured todetect a temperature change within the luminal organ from a firsttemperature to a temperature indicative of an injection of a bolus of asolution having a known conductivity; and at least two electrodes alongthe elongated body wherein at least one of the at least two electrodesis/are located distal to the thermistor, the at least two electrodesconfigured to obtain multiple conductance measurements within theluminal organ in connection with the injected solution and based uponthe detected temperature change prior to dilution of the bolus and atleast until a threshold temperature is reached.
 13. The device of claim12, configured so that a parallel conductance can be calculated based inpart upon the temperature change obtained by the thermistor, at leastone conductance measurement of the multiple conductance measurementsobtained by the at least two electrodes, and the conductivity of theinjected solution.
 14. The device of claim 12, wherein the at least twoelectrodes comprises at least two detection electrodes, and wherein thedevice further comprises at least two excitation electrodes, wherein twoof the at least two detection electrodes are positioned in between twoof the at least two excitation electrodes.
 15. The device of claim 14,wherein at least one excitation electrode is/are in communication with acurrent source capable of supplying electrical current to the at leastone excitation electrode.
 16. The device of claim 12, wherein theelongated body is selected from the group consisting of a wire and acatheter.
 17. The device of claim 12, wherein the device defines a lumentherethrough and further comprises a suction/infusion port locatedproximal to the at least one electrode, wherein the suction/infusionport is in communication with the lumen, thereby enabling injection of asolution into a luminal organ through the suction/infusion port.
 18. Thedevice of claim 12, wherein at least one of the at least two electrodesand the thermistor share an electrical wire connection capable ofproviding current to the at least one of the at least one electrodes andthe thermistor.
 19. A system configured to obtain conductance datawithin a luminal organ, comprising: a detection device, comprising: anelongated body having a thermistor located thereon, the thermistorconfigured to detect temperature data including a temperature changewithin the luminal organ from a first temperature to a temperatureindicative of an injection of a bolus of a solution having a knownconductivity; and at least two electrodes along the elongated bodywherein at least one of the at least two electrodes is/are locateddistal to the thermistor, the at least two electrodes configured toobtain multiple conductance measurements within the luminal organ inconnection with the injected solution and based upon the detectedtemperature change prior to dilution of the bolus and at least until athreshold temperature is reached; and a data acquisition and processingsystem operably coupled to the device and capable of (a) receiving thetemperature data from the thermistor in connection with the injection ofthe bolus, and (b) obtaining the multiple conductance measurements fromthe at least two electrodes while receiving the temperature data. 20.The system of claim 19, wherein the elongated body is selected from thegroup consisting of a wire and a catheter, and wherein the dataacquisition and processing system is further operable to calculate aparallel tissue conductance based in part upon at least one conductancemeasurement of the multiple conductance measurements and the knownconductivity of the solution.